IDWeek 2019 News Network: Current Treatment Landscape for Pneumonia

Segment Description: George Sakoulas, MD, UC San Diego School of Medicine, discusses the current treatment landscape for community acquired bacterial pneumonia and comments on new guidelines for treatment.

George Sakoulas, MD: Some of our newer agents, omadacycline and delafloxacin, have obtained almost simultaneous approvals or simultaneous approvals for both ABSSSI and community acquired bacterial pneumonia (CABP). That speaks to 2 things…1) the illnesses are largely driven by gram-positive agents. So in skin infections, you have Staph aureus and Streptococcus, either group A or group B or other beta-hemolytic Strep. In community acquired bacterial pneumonia, again, it’s a Streptococcus pneumoniae followed by Staph aureus. Gram-negatives take on a more important role in both of those illnesses as the patient becomes more comorbid, more immunocompromised, and so they have relatively similar spectra to cover: Staphs and Streps in both settings. Skin, pneumonia, and UTI are the 3 most common infections that we see in hospitals. And so getting drugs through the approval process through registration trials, it's easier to go for infections that are very easy to enroll in, ie, common ones like pneumonia and skin, in order to get a drug onto the marketplace rather than starting with an illness that might actually have a larger medical need for newer antibiotics but would be harder to enroll patients in, like bacteremias or osteomyelitis and so on. And so hence the very similar crossover and simultaneous approval for drugs with community acquired bacterial pneumonia and ABSSSI.

Community acquired bacterial pneumonia is an interesting entity at the moment. We have lots of agents available. Traditionally, we've had fluoroquinolones that have essentially been the cornerstone of that market. But there's been recent concerns with fluoroquinolones, concerns of glycemic control, QT prolongation, [Clostridioides] difficile concerns, tendon ruptures, now aortic ruptures. In fact, the FDA has actually taken a few steps to issue warnings, most recently with aortic rupture warnings back last December, really leaving physicians who are prescribing fluoroquinolones and patients with community acquired bacterial pneumonias and comorbidities balancing these dark clouds hanging in the distance, hoping that the patient doesn't have any complications. And the one that really comes to mind in real time is C difficile, because C difficile is clearly a risk with fluoroquinolone use. Elderly patients are the ones that get pneumonia, they're also the ones at highest risk for forgetting C difficile. So I think the most difficult dilemma that clinicians are faced when treating pneumonia, you want to try to use a, perhaps a non-quinolone, because you don't want to go through the risk that I just mentioned, but at the same time you don't want to miss the pathogen by using a drug like tetracycline that doesn’t have really good pneumococcal activity. So that that really is the sort of dilemma facing physicians, particularly in an outpatient setting, or when you're discharging a patient home after a short hospital stay for pneumonia in selecting therapy.

The new guidelines for CABP were recently released within the last few days. I looked them over and there's been some updates with them. There are comments on procalcitonin, which we're not on the old guidelines because the old guidelines were issued before procalcitonin, when it became a mainstream option for clinicians, and the comment about not using it to decide whether a patient needs or does not need antibiotics. I think an important point in there that was highlighted was the use of sequential radiographs. A lot of clinicians chase follow up X-rays that wind up getting them into trouble, perhaps overtreating because patients have already graphic lag so issuing recommendations for not getting follow up chest X-rays which might have been a traditional practice for many physicians, I think is a very positive aspects. The use of glucocorticoids also was argued against in most cases except severe sepsis.

What was a little bit disappointing was the lack of mention of the new agents and the role they might have played like omadacycline, delafloxacin, the pleuromutilin lefamulin. And they were all recently approved options that clinicians have and they were completely left off the treatment guidelines. I think clinicians when facing these guidelines and looking at these guidelines might need some guidance and incorporating these and it would have been nice if these guidelines address that, how they would be incorporated, for example, balancing the risk of C difficile with quinolones, and which high risk patients might benefit from some these newer agents despite their higher costs, so that was lacking, I think it speaks to the long process that leads to guidelines being ultimately published, probably one of the reasons why many of us don't refer to textbooks anymore because textbooks, by the time they get written up and put in print, they're outdated. And it almost appears that the guidelines sort of fell victim to that kind of process as well. It's the long cumbersome process of getting them to print kind of left them missing out on the new developments and clinicians’ guidance, so, hopefully it won't be too long before the new agents are addressed in that decision process.